Plasma NGAL levels in stable kidney transplant recipients and the risk of allograft loss

BACKGROUND: The object of this study was to investigate the utility of Neutrophil gelatinase-associated lipocalin (NGAL) and Calprotectin (CPT) to predict long-term graft survival in stable kidney transplant recipients (KTR). METHODS: 709 stable outpatient KTR were enrolled >2 months post-transplant. The utility of plasma and urinary NGAL (pNGAL, uNGAL) and plasma and urinary CPT at enrollment to predict death-censored graft loss (GL) was evaluated during a 58-month follow-up. RESULTS: Among biomarkers, pNGAL showed best predictive ability for graft loss and was the only biomarker with an AUC > 0.7 for GL within 5 years. Patients with GL within 5 years (n=49) had a median pNGAL of 304[IQR 235-358] versus 182[IQR 128 -246]ng/ml with surviving grafts (p<0.001). Time-dependent Receiver operating characteristic analyses at 58 months indicated an Area-Under-the-Curve (AUC) for pNGAL of 0.795, serum creatinine (sCr) based estimated glomerular filtration rate (eGFR) CKD EPI had an AUC of 0.866. pNGAL added to a model based on conventional risk factors for GL with death as competing risk (age, transplant age, presence of donor specific antibodies, presence of proteinuria, history of delayed graft function) had a strong independent association with GL (subdistribution Hazard ratio (sHR) for binary log transfomed pNGAL (log2 (pNGAL)) (3.4 95% CI 2.24-5.15), p<0.0001). This association was substantially attenuated when eGFR was added to the model (sHR for log2 (pNGAL) 1.63 95% CI 0.92-2.88, p=0.095). Category-free net reclassification improvement of a risk model including log2(pNGAL) additionally to conventional risk factors and eGFR was 54.3% (95% CI 9.2 to 99.3%) but C-statistic did not improve significantly. CONCLUSIONS: pNGAL was an independent predictor of renal allograft loss in stable KTR from one transplant center but did not show consistent added value when compared to baseline predictors including the conventional marker eGFR. Future studies in larger cohorts are warranted

Species richness is more important for ecosystem functioning than species turnover along an elevational gradient

Many experiments have shown that biodiversity enhances ecosystem functioning. However, we have little understanding of how environmental heterogeneity shapes the effect of diversity on ecosystem functioning and to what extent this diversity effect is mediated by variation in species richness or species turnover. This knowledge is crucial to scaling up the results of experiments from local to regional scales. Here we quantify the diversity effect and its components-that is, the contributions of variation in species richness and species turnover-for 22 ecosystem functions of microorganisms, plants and animals across 13 major ecosystem types on Mt Kilimanjaro, Tanzania. Environmental heterogeneity across ecosystem types on average increased the diversity effect from explaining 49% to 72% of the variation in ecosystem functions. In contrast to our expectation, the diversity effect was more strongly mediated by variation in species richness than by species turnover. Our findings reveal that environmental heterogeneity strengthens the relationship between biodiversity and ecosystem functioning and that species richness is a stronger driver of ecosystem functioning than species turnover. Based on a broad range of taxa and ecosystem functions in a non-experimental system, these results are in line with predictions from biodiversity experiments and emphasize that conserving biodiversity is essential for maintaining ecosystem functioning. The authors measure numerous ecosystem functions across an elevational gradient on Mt Kilimanjaro and find that species richness impacts function more than species turnover across sites. They also show that variation in species richness impacts ecosystem functioning more strongly at the landscape scale than at the local scale